DNA Virus – Carcinogenesis

by Carlo Raj, MD

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    00:01 At this juncture, you may want to take a look at that flow chart that I began our discussion with.

    00:08 Do not lose sight of what we are trying to accomplish. Our objective for that flow chart was to take a normal cell, and then upon exposure various elements such as chemicals that I walked you through including arsenics such as chromium, such as nitrosamines so on and so forth. The patient may develop a cancer or if the patient is being exposed to certain viruses here may develop cancer. Let's talk about HPV now.

    00:38 Our topic is a DNA virus that the patient has been exposed to and, he or she, develops cancer. Now HPV is a big deal.

    00:49 Listen. With HPV you should be thinking about sexually transmitted infection right, STI.

    00:56 With HPV could be male or female put them both together. And with HPV you should be thinking about the higher strains not the lower. My topic is cancer. HPV 16,18,31 and 33. And with HPV, in a female you begin with the following.

    01:15 There might be vulva issues. So there might be squamous cell cancer of the vulva. You keep going.

    01:22 There might be issues within the vagina and in the cervix. Would you tell me the part of the cervix that's facing you.

    01:29 Meaning, facing you as a clinician when you do a pelvic exam. That's the exocervix. What kind of cells is your exocervix? Squamous. There you are in the transformation zone. Are you there? Put yourself in the cervix, the transformation zone.

    01:46 That which is facing the external world, exocervix is squamous. That which is facing the uterus, endocervix is the columnar.

    01:56 That's your transformation zone. Now you tell me quickly what is it within the vagina that allows for the cells to remain squamous? The decreased pH. What is the bacteria that remains within the vagina that provides that type of acidic environment? Lactobillus. Keep all that in mind because with HPV, 85% of the time if the patient. Cervical cancer, where is your patient most likely coming from? Developed or developing countries? Good. Developing countries. 85% of the time if you are in the transformation zone, the virus has a choice of either becoming a adenocarcinoma or a squamous cell cancer.

    02:41 85% of the time what is it going to choose? Squamous. Not only that. With HPV maybe you have a couple that practices oral sex and felatio so on and so forth. So there is every possibility that HPV might enter the head and the neck. May result in head and neck cancer. Guess what kind. Squamous. Now unbelieveably you've learned in Immunology that you even have a vaccination for this and it's called Gardasil. You are guarding against squamous intra epithelial lesion. Where? Vulva, cervix, head and neck.

    03:22 Is'nt that amazing. That you actually have a vaccine that may prevent certain cancers from taking place. And then molecularly, if you remember from micro, with HPV these strains contain E6 and E7. What do they do? Knock out the tumor suppressor gene p53 and what's the other one? Rb. E6, E7 respectively. HPV, you should know everything about HPV. What about the lower strain? Condyloma Acuminata. What? Remember warts? That's your condyloma acuminata. Know everything about HPV. Low strain, high strain.

    04:04 Our topic, high strain. Alright, let's move on to EBV. EBV is all over the place. Oh my goodness. Usually infects B-cells.

    04:14 And if it's B-cells then what kind of CD are you looking for? Good. CD 19,20,21. You should be focusing upon 21.

    04:22 These are epithelial cells of nasopharynx. Nasopharynx, CD 21. So if that's the case, is it possible that EBV might give rise to nasopharyngeal cancer. Sure. Who's your population? Far east. Japan and company. Our topic with EBV, associated highly with Burkitt lymphoma. Translocation 8,14. t(8;14). By the time we are done with our discussion of cancer we will have gone through three major translocation that contains 14. t(8;14), t(14;18), t(11;14).

    05:00 Once again, t(8;14) Burkitt. t(14;18) Follicular. t(11;14) I'm sorry, what? Good. Mantle cell.

    05:08 Burkitt lymphoma. Specifically what if I give you a African American boy. The boards will give you an African American boy.

    05:16 Actually not even African American, literally from Africa, a child. Where is Burkitt lymphoma affecting that African child? Mandible.

    05:28 That's the one EBV is associated with more so. We call that the endemic type. The non-endemic type, when we'll come to that well, that will be the North American type, sporadic. Not so much with EBV. B-cell lymphoma in immunocompromised. Hodgkin's big time.

    05:45 The most common Hodgkin is not mixed cellularity. The most common Hodgkin's would be the sclerosing type.

    05:52 Also associated with EBV. Mixed cellularity as well. What do you have to find pathologically, on biopsy, to diagnose Hodgkin's. Without this you cannot call it Hodgkin's. Reed?Sternberg cell. What is it? It's a B-cell. It's a lymphoma. And nasopharyngeal. We began talking about EBV and CD 21. Population here, far east.

    06:20 Our topic is DNA viruses. So far, HPV, EBV then you have Hepatitis B. Why is there no Hepatitis C here? Because Hepatitis C is a RNA virus. So next when we talk about RNA, we'll talk about Hepatitis C. Hepatitis B, could be associated with chronicity, could be associated with hepatocellular carcinoma of the liver.

    06:44 RNA viruses that are important for you of developing cancer. Whenever you think about hepatitis C you should be thinking about chronicity. Hence associated with hepatocellular carcinoma.

    07:01 Then you have an interesting one here. It's called HTLV-1. Human T-cell Lymphotrophic virus 1.

    07:10 You focus upon the letter 'T'. HTLV virus 1 may give rise to T-cell leukaemia/lymphoma. The gene here that you will have to know is Tax. 'T'. HTLV 1. Adult T-cell leukaemia/lymphoma. Tax.

    07:37 Know this three for your step, you will be in good shape. These are important RNA viruses. There are a bunch more.

    07:43 But at least know this two associated with cancer. Bacteria associated with cancer. Obviously this bring us to H.pylori. Helicobacter Pylori.

    07:57 Helicobacter Pylori loves to live either in the antrum of the stomach or it loves to live in the first part of the duodenum.

    08:04 So, right around here right. In that area. The antrum and the first part of the duodenum. H.pylori, you talked about urease you know that it produces a forcefield. This thing is like a superhero. But, it actually a supervillain, isn't it.

    08:17 It creates a forcefield composed of alkaline. H.pylori. And at some point with H.pylori it might give rise to a gastric adenocarcinoma.

    08:30 And that's called intestinal type. And Helicobacter pylori might then give rise to a second gastric cancer here and it's called a MALToma (Mucuous associated lymphoid tissue), welcome to a B-cell type. Why am I emphasizing B? Because in the gut, in the GI system, if it's any type of lymphoma that the patient is going to develop it is going to a B-cell.

    08:54 A extranodal Non-Hodgkin's lymphoma, we call this a diffuse large B-cell lymphoma.

    09:03 Can be reversed with treatment. That is unbelievable isn't it. The fact that you can actually treat a cancer by giving H.pylori. Excuse me, you can treat a cancer by treating H.pylori. Antibiotics, kills off the cancer.

    09:19 Of course the boards will love this. And you're thinking about drugs. Such as H2-blocker, maybe your clarithromycin, antibiotic bismuth is in there as well. And it's important that we pay attention to the management when the time is right.

    09:31 You also have a PPI as well.

    About the Lecture

    The lecture DNA Virus – Carcinogenesis by Carlo Raj, MD is from the course Cellular Pathology: Basic Principles.

    Included Quiz Questions

    1. HPV 16, 18
    2. HPV 6, 11
    3. HBV 16, 18
    4. EBV
    5. HPV 32, 34
    1. Liver carcinoma
    2. Burkitt lymphoma
    3. B-cell lymphoma
    4. Hodgkin disease
    5. Nasopharyngeal carcinoma
    1. CD21
    2. Nasopharyngeal epithelium
    3. EBV viral receptor
    4. Damaged B cell receptors
    5. CD14
    1. HTLV-1
    2. EBV
    3. Hepatitis C
    4. H. pylori
    5. HPV 16, 18
    1. Gastric carcinoma
    2. T cell lymphoma
    3. Liver cancer
    4. Hodgkin disease
    5. Nasopharyngeal carcinoma

    Author of lecture DNA Virus – Carcinogenesis

     Carlo Raj, MD

    Carlo Raj, MD

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